Feedback control of ultrafiltration to prevent hypotension

ABSTRACT

A method and system for the extracorporeal treatment of blood to remove fluid from the fluid overloaded patient is disclosed that non-invasively measures an oxygen level in the venous blood. The oxygen blood level is used to detect when hypotension is about to occur in a patient. The oxygen level measurements are used as feedback signals. These feedback signals are applied to automatically control the rate of fluid extraction to achieve the desired clinical outcome and avoid precipitating a hypotensive crisis in the patient.

FIELD OF INVENTION

The present invention relates to an apparatus for the extracorporealtreatment of blood and more specifically to the automatic control offluid removal from the blood of patients suffering from fluid overloadand averting therapy induced hypotension.

BACKGROUND OF THE INVENTION

Renal Replacement Therapy (RRT) has evolved from the long, slowhemodialysis treatment regime of the 1960's to a diverse set of therapyoptions, the vast majority of which employ high permeability membranedevices and ultrafiltration control systems.

Biologic kidneys remove metabolic waste products, other toxins, andexcess water. They also maintain electrolyte balance and produce severalhormones for a human or other mammalian body. An artificial kidney, alsocalled a hemodialyzer or dialyzer, and attendant equipment and suppliesare designed to replace the blood-cleansing functions of the biologickidney. At the center of artificial kidney design is a semipermeablefilter membrane that allows passage of water, electrolytes, and solutetoxins to be removed from the blood. The membrane retains in the blood,the blood cells, plasma proteins and other larger elements of the blood.

Over the last 15 years, the intended use of the RRT equipment the systemhas evolved into a subset of treatment alternatives that are tailored toindividual patient needs. They include ultrafiltration, hemodialysis,hemofiltration, and hemodiafiltration, all of which are delivered in arenal care environment, as well as hemoconcentration, which is typicallydelivered in open heart surgery. Renal replacement therapies may beperformed either intermittently or continuously, in the acute or chronicrenal setting, depending on the individual patient's needs.

Ultrafiltration involves the removal of excess fluid from the patient'sblood by employing a pressure gradient across a semipermeable membraneof a high permeability hemofilter or dialyzer. For example, removal ofexcess fluid occurs in hemoconcentration at the conclusion ofcardiopulmonary bypass surgery. Hemodialysis involves the removal oftoxins from the patient's blood by employing diffusive transport throughthe semipermeable membrane, and requires an electrolyte solution(dialysate) flowing on the opposite side of the membrane to create aconcentration gradient. A goal of dialysis is the removal of waste,toxic substances, and/or excess water from the patients'blood. Dialysispatients require removal of excess water from their blood because theylack the ability to rid their bodies of fluid through the normal urinaryfunction.

One of the potential risks to health associated with RRT is hypotension,which is an abnormal decrease in the patient's blood pressure. Anabnormally high or uncontrolled ultrafiltration rate may result inhypovolemic shock, hypotension, or both. If too much water is removedfrom the patient's blood, such as might occur if the ultrafiltrationrate is too high or uncontrolled, the patient could suffer hypotensionand/or go into hypovolemic shock. Accordingly, RRT treatments must becontrolled to prevent hypotension.

Alternatively, a patient may experience fluid overload in his blood, asa result of fluid infusion therapy or hyperalimentation therapy. Certainkinds of RRT machine failures may result in fluid gain rather than fluidloss. Specifically, inverse ultrafiltration may result in unintendedweight gain of a patient and is potentially hazardous. Uncontrolledinfusion of fluid by whatever mechanism into the patient could result influid overload, with the most serious acute complication being pulmonaryedema. These risks are similar in all acute and chronic renalreplacement therapies (ultrafiltration, hemodialysis, hemofiltration,hemodiafiltration, hemoconcentration). Monitoring patients to detectexcessive fluid loss is needed to avoid hypotension.

Rapid reduction in plasma or blood volume due to excessiveultrafiltration of water from blood may cause a patient to exhibit oneor more of the following symptoms: hypovolemia-hypotension, diaphoresis,cramps, nausea, or vomiting. During treatment, plasma volume in thepatient's blood would theoretically remain constant if the plasmarefilling rate equaled the UF (ultrafiltration) rate. However, refillingof the plasma is often not completed during a RRT session. The delay inrefilling the plasma can lead to insufficient blood volume in a patient.

There appears to be a “critical” blood volume value below which patientsbegin to have problems associated with hypovolemia (abnormally decreasedblood volume). Fluid replenishing rate is the rate at which the fluid(water and electrolytes) can be recruited from tissue into the bloodstream across permeable walls of capillaries. This way blood volume ismaintained relatively constant. Most of patients can recruit fluid atthe rate of 500 to 1000 mL/hour. When patients are treated at a fasterfluid removal rate, they begin to experience symptomatic hypotension.

Hypotension is the manifestation of hypovolemia or a severe fluidmisbalance. Symptomatically, hypotension may be experienced by thepatient first as light-headedness. To monitor patients for hypotension,non-invasive blood pressure monitors (NIBP) are commonly used duringRRT. When detected early, hypotension resulting from the excessive lossof fluid is easily reversed by giving the patient intravenous fluids.Following administering fluids the RRT operator can adjust theultrafiltration rate to make the RRT treatment less aggressive.

Ultrafiltration controllers were developed specifically to reduce theoccurrence of hypotension in dialysis patients. Ultrafiltrationcontrollers can be based on approximation from the known trans-membranepressure (TMP), volume based or gravity based. Roller pumps and weightscales are used in the latter to meter fluids. Ultrafiltrationcontrollers ensure the rate of fluid removal from a patient's blood isclose to the fluid removal setting that was selected by the operator.However, these controllers do not always protect the patient fromhypotension. For example, the operator may set the fluid removal ratetoo high. If the operator setting is higher than the patient's fluidreplenishing rate, the operator should reduce the rate setting when thesigns of hypotension manifest. If the excessive rate is not reduced, thepatient may still suffer from hypotension, even while the controlleroperates properly.

Attempts were made during the last two decades to develop monitors thatcould be used for feedback control of dialysis machine parameters, suchas dialysate concentration, temperature, and ultrafiltration rate andultrafiltrate volume. Blood volume feedback signals have been proposedthat are based on optical measurements of hematocrit, blood viscosityand blood conductivity. Real time control devices have been proposedthat adjust the ultrafiltration rate to maintain the blood volumeconstant, and thereby balance the fluid removal and fluid recruitmentrates. None of these proposed designs led to significantcommercialization owing to the high cost of sensors, high noise tosignal ratio or lack of economic incentive for manufacturers. Inaddition, many of these proposed systems required monitoring of patientsby highly trained personnel.

Controllers that protect from hypotension are especially needed forpatients suffering from fluid overload due to chronic Congestive HeartFailure (CHF). In CHF patients, fluid overload typically is notaccompanied by renal failure. In these patients mechanical solute(toxins) removal is not required. Only fluid (plasma water) removal isneeded. Ideal Renal Replacement Therapy (RRT) for these patients is SlowContinuous Ultrafiltration (SCUF) also known as “Ultrafiltration withoutDialysis”.

SCUF must be controlled to avoid inducing hypotension in the patient.Due to their poor heart condition, CHF patients are especiallyvulnerable to hypotension from excessively fast fluid removal. Theclinical treatment objective for these patients can be formulated as:fluid removal at the maximum rate obtainable without the risk ofhypotension. This maximum rate is equivalent to fluid removal at themaximum rate at which the vascular volume can be refilled from tissue.This maximum rate for CHF patients is typically in the 100 to 1,000mL/hour range. The rate can vary with the patient's condition and isalmost impossible to predict. The rate can also change over the courseof treatment, especially if the objective of treatment is to remove 2 to10 liters of fluid.

Hypotension in CHF patients often results from a decrease of the cardiacoutput of the patient. Cardiac output is the volume of blood that isejected per minute from the heart as a result of heart contractions. Theheart pumps approximately 4-8 L/min in a normal person. In a CHF patientcardiac output most often decreases because the heart is subject to areduction of filling pressure. This dependency on the filling pressureis a well-known clinical consequence of the deterioration of the heartmuscle during CHF. In a healthy person when the heart filling pressureis lowed, the heart will compensate and maintain cardiac output byworking (e.g. pumping) harder. Filling pressure is the blood pressure inthe right atrium of the heart. This pressure is approximately equal tothe patient's venous pressure measured elsewhere in a great or centralvein (such as vena cava) and corrected for gravity. In a fluidoverloaded CHF patient Central Venous Pressure (CVP) is typicallybetween 10 and 20 mmHg. If this pressure drops by 5 to 10 mmHg, thepatient is likely to become hypotensive soon.

The danger of hypotension as a consequence of excessive fluid removalduring dialysis and other extracorporeal blood treatments has beenrecognized. U.S. Pat. No. 5,346,472 describes a control system toprevent hypotension that automatically adjusts the sodium concentrationadded to the dialysate by infusing a hypertonic or isotonic salinesolution in response to operator input or patient's request based onsymptoms. European patent EU 0311709 to Levin and Zasuwa describesautomatic ultrafiltration feedback based on arterial blood pressure andheart rate. U.S. Pat. No. 4,710,164 describes an automaticultrafiltration feedback device based on arterial blood pressure andheart rate. U.S. Pat. No. 4,466,804 describes an extracorporealcirculation system with a blood oxygenator that manipulates thewithdrawal of blood to maintain CVP constant. U.S. Pat. No. 5,938,938describes an automatic dialysis machine that controls ultrafiltrationrate based on weight loss or the calculated blood volume change. Latemodel AK200 dialysis machines from Gambro (Sweden) include an optionalblood volume monitor called BVS or Blood Volume Sensor. This sensor isoptical and in fact measures blood hematocrit or the concentration ofred blood cells in blood. Since dialysis filter membranes areimpermeable to blood cells, increased hematocrit signifies the reductionof the overall blood volume. The BVS sensor is not included in afeedback to the machine and is used to help the operator assess the rateof fluid removal.

U.S. Pat. No. 5,346,472 describes a mixed venous oxygen saturationresponsive system for treating a malfunctioning heart. By sensing thechange of the oxygen content in the venous blood the system adjusts theoperation of a heart pacemaker. However, venous saturation of blood hasnever been used in adjusting an extracorporeal blood therapy for fluidremoval such as ultrafiltration, hemofiltration or dialysis.

Other devices have been proposed that use arterial pressure as afeedback to the ultrafiltration controller to avoid hypotension.Automatic Non-Invasive Blood Pressure (NIBP) monitor feedback was usedas a control system input. NIBP measures systolic and diastolic arterialblood pressure by periodically inflating a blood pressure cuff aroundthe patient's arm or leg. Acoustic or oscillatory methods detect thepressure level at which blood vessels collapse.

This level approximates systemic arterial blood pressure. Closed loopdialysis or fluid removal devices designed around this principle haveseveral inherent deficiencies, including:

a) NIBP is inaccurate. Errors of up to 20 mmHg can be expected in thesystem. To avoid system oscillations and false alarms, the feedbackwould have to be slow and heavily filtered.

b) NIBP is not continuous, but is rather based on periodic pressuremeasurements. If the blood pressure cuff were inflated more frequently,less than every 15 minutes a patient would experience significantdiscomfort. Also, blood vessels change their elasticity from thefrequent compressions of the blood cuff. This change in elasticity canadd to the inaccuracy of cuff pressure measurements.

c) The arterial pressure in a CHF patient does not drop immediatelyfollowing the reduction of cardiac output. It may take considerable timefor a CHF patient to exhaust their cardiac reserve. By that time, thehypotension would have already occurred and its reversal would requiremedical intervention. Accordingly, hypotension may occur before NIBPdetects it.

d) In a CHF patient, arterial blood pressure is maintained by the bodyto protect the brain. Neurohormonal signals are sent in response tobaroreceptors that cause vasoconstriction of blood vessels to legs,intestine and kidneys. By sacrificing other body organs needs, arterialblood pressure to the brain can be kept constant at the expense ofreduced blood flow to organs while the cardiac output is reduceddramatically.

Altogether, hypotension in a CHF patient can create a dangeroussituation when the arterial blood pressure is apparently normal, whilethe overall condition of the patient is worsening. By the time the NIBPmeasurement has detected hypotension, serious medical intervention maybe needed.

It is desired to have a feedback based control system that willcontinuously and automatically manipulate the ultrafiltration rate toachieve optimal ultrafiltration. In such a system, fluid is removedrapidly and without the risk of hypotension. It is also desired, in theapplication to CHF patients, to anticipate and correct the onset of thecondition that before it is manifested by the reduction of arterialpressure.

SUMMARY OF INVENTION

A method and system has been developed for removing fluid from a fluidoverloaded patient at a maximum safe rate that does not require humanmonitoring and interaction. The system senses oxygen saturation in apatient's venous blood as being indicative of conditions that causehypotension. By monitoring oxygen saturation, the system detects thedecrease of cardiac output that precedes the onset of hypotension andmaintains a safe filtration rate by reducing or periodically turning offultrafiltration when the oxygen saturation feedback signal indicatesthat hypotension may occur. Using the system that has an oxygensaturation feedback signal, hypotension is averted before it occurs.

A real time feedback system has been developed that:

a) Allows for an optimal rate of fluid removal in vulnerable CHFpatients by automatically measuring and monitoring venous blood oxygenlevel, e.g., SvO₂, as indicators of the potential of hypotension.

b) Prevents episodes of hypotension so that fluid removal treatment canbe conducted under minimal supervision.

c) Uses robust and inexpensive measurement system for monitoring thephysiological blood parameters.

A method and system has been developed for removing fluid from a fluidoverloaded patient at a maximum safe rate that does not require humanmonitoring and interaction to avoid hypotension. The system uses aphysiologic blood variable, such as the oxygen level in blood, as beingindicative of conditions that cause hypotension. The system maintainsthe physiological variable at a safe level by reducing or periodicallyturning off ultrafiltration. In this way hypotension is averted beforeit occurs.

In some instances, the absolute value of a physiologic blood variable orits significance is difficult to determine accurately. However, thechange of the variable may be accurately determined, even if theabsolute value of the variable is difficult to measure. Duringultrafiltration treatment, the amount of change in a variable may bedetermined from a level of the variable established at the beginning oftreatment. For example, a 20% drop of cardiac output during treatment iseasier to detect than determining an absolute value for cardiac outputor an absolute cardiac output value that is indicative of insufficientoutput. In particular, detecting a substantial drop of 20% in cardiacoutput may be more readily determined, than detecting when cardiacoutput falls below a 3 liter/minute threshold. Thus, an amount ofchange, rate of change and/or percentage change in a physiological bloodparameter may be used to detect hypotension.

Mixed Venus Oxygen Saturation (SvO₂) provides a good estimate of themetabolic oxygen supply and demand and is related to cardiac output.When the cardiac output is decreased or when the cardiac output cannotcompensate for increased oxygen utilization, the mixed venous oxygencontent falls. SvO₂ represents the end result of both oxygen deliveryand consumption at the tissue level for the entire body. Clinically,SvO₂ can be the earliest indicator of acute deterioration and is closelyrelated to cardiac output. Venous blood is normally relativelyunoxygenated, having not yet traveled through the lungs, with asaturation of 60-80%. The level of SvO₂ is a function of how much oxygenis being extracted from the blood by the organs. SvO₂ is an indicator ofthe supply and demand of oxygen to the tissues.

Arterial oxygen delivery is the product of cardiac output (QT) andarterial oxygen content (Cao₂); a reduction in either QT or Cao₂threatens the adequacy of oxygen delivery. In either case (reduced QT orreduced CaO2), lactic acidosis and death will ensue if tissue oxygenuptake (Vo₂) is not maintained by the product of QT times the(Cao₂-Cvo₂). When cardiac output is decreased or when cardiac outputcannot compensate for a decrease in Cao₂, the mixed venous oxygencontent (and thus SvO₂ and Pvo₂) will fall. Thus, SvO₂ is a barometer ofthe adequacy of oxygen delivery (QT×Cao₂) for the body's oxygen needs.

During RRT treatment of a fluid overloaded patient, SvO₂ should remainwithin normal ranges, and change very little. Hemoglobin content andoxygen consumption should vary only slightly during the 4-8 hour oftreatment for fluid overload. A sudden decrease of SvO₂ is most likelyan indication of sudden drop of cardiac output and a precursor ofhypotension. Accordingly, detecting a substantial change in SvO₂ levelscan be used as an indicator of hypotension and used to reduce a bloodtreatment rate, such as an ultrafiltration rate.

Venous blood oxygen saturation is an accepted indicator of the remainingoxygen content in the venous blood. Hemoglobin (Hb), an intracellularprotein, is the primary vehicle for transporting oxygen in the blood.Hemoglobin is contained in erythrocytes, more commonly referred to asred blood cells. Oxygen is also carried (dissolved) in plasma, but to amuch lesser degree. Under conditions of increased oxygen utilization bythe tissues, oxygen that is bound to the hemoglobin is released intobody tissue. When the patient inhales, oxygen from the air is absorbedin the blood, as the blood passes through lungs. Each hemoglobinmolecule in the blood has a limited capacity to bond to oxygenmolecules. Oxygen saturation is the degree to which the capacity to bindto oxygen is actually filled by oxygen bound to the hemoglobin. Oxygensaturation, when expressed as a percentage, is the ratio of the amountof oxygen molecules bound to the hemoglobin, to the oxygen carryingcapacity of the hemoglobin. The oxygen carrying capacity is determinedby the amount of hemoglobin present in the blood.

Moreover, SvO₂ changes can be measured non-invasively using pulseoxymetry. Non-invasive photoelectric pulse oximetry has been previouslydescribed in U.S. Pat. Nos. 4,407,290, 4,266,554, 4,086,915, 3,998,550and 3,704,706. Pulse oxymeters are commercially available from NellcorIncorporated, Pleasanton, Calif., U.S.A., and other companies forintegration in medical devices.

Pulse oxymeters typically measure and display various blood flowcharacteristics including but not limited to blood oxygen saturation ofhemoglobin in arterial blood. The oxymeters pass light through human oranimal body tissue where blood perfuses the tissue such as a finger, anear, the nasal septum or the scalp, and photoelectrically sense theabsorption of light in the tissue. The amount of light absorbed is thenused to calculate the amount of blood constituent being measured. Thelight passed through the tissue is selected to be of one or morewavelengths that is absorbed by the blood in an amount representative ofthe amount of the blood constituent present in the blood. The amount oftransmitted light passed through the tissue will vary in accordance withthe changing amount of blood constituent in the tissue and the relatedlight absorption.

For example, the Nellcor N-100 oximeter is a microprocessor controlleddevice that measures oxygen saturation of hemoglobin using light fromtwo light emitting diodes (“LED's”), one having a discrete frequency ofabout 660 nanometers in the red light range and the other having adiscrete frequency of about 925 nanometers in the infrared range.

Since in a RRT machine blood circulates outside of the body through atransparent plastic tube, the photometric method of oximetry can beeasily adapted for the application. Light emitting LED's and the lightreceiving device can be placed on the opposite sides of the tube. Devicecan be calibrated to subtract the affects of the tubing on themeasurement.

During the fluid removal treatment in a CHF patient, central venousblood is not always available. In some cases in acute RRT treatment socalled central venous catheters are used for blood withdrawal andreturn. These catheters are advanced from a femoral, jugular orsubclavian veins. The tip of the catheter is advanced deep into the bodyuntil central access to venous blood is established. Such catheters candraw true mixed venous blood similar in composition to the blood in theright atrium of the heart. Such catheters are associated with high risksthat are not always acceptable.

It is desired to have a device for treatment of fluid overloaded CHFpatients that will only draw blood from a peripheral vein that is alwaysavailable. Suitable peripheral veins are the veins in the arm of thepatient. The tip of the catheter can be located in a relatively smallvein in the middle of the arm or could be advanced close to theshoulder. In the latter case, if the tip has past venous valves, theblood in the extracorporeal circuit will be similar in composition tothe blood in a central vein. Although oxygen saturation in the bloodfrom a peripheral vein reflects both global and local organ oxygenextraction, and can be used to detect low cardiac output based onmeasurements of SvO₂. Accordingly, SvO₂ changes can be monitored duringblood treatments that use central, mid line (closer to the shoulder) andperipheral blood access.

BRIEF DESCRIPTION OF THE DRAWINGS

The attached drawings and associated written description disclose anexemplary embodiment of the present invention:

FIG. 1 shows a high level schematic diagram of an ultrafiltration systemthat detects oxygen level in the blood.

FIG. 2 illustrates a non-invasive sensor system for measuring venousoxygen saturation in a blood filled tube by optical oximetry.

FIG. 3 shows a curve of venous oxygen saturation measurements over timeduring a course of fluid extraction therapy in a fluid overloadedpatient undergoing fluid removal.

FIG. 4 shows a curve of venous oxygen saturation expressed as apercentage of the baseline value.

FIG. 5 illustrates a method of controlling ultrafiltration byestablishing a predetermined deviation from baseline value of oxygensaturation.

FIG. 6 illustrates design of the controller for ultrafiltrationapparatus.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

FIG. 1 shows a high level schematic diagram of an ultrafiltrationsystem, such as is disclosed in commonly-owned (U.S. patent applicationSer. No. 09/660,195, filed Sep. 12, 2000), entitled “Blood Pump Having ADisposable Blood Passage Cartridge With Integrated Pressure Sensor”, andU.S. Pat. No. 6,585,675 (U.S. patent application Ser. No. 09/703,702,filed Sep. 12, 2000), entitled “Method And Apparatus For BloodWithdrawal And Infusion Using A Pressure Controller” and filed Nov. 2,2000, both of which applications are incorporated by reference in theirentirety.

Blood is withdrawn from the vein 103 of a human or other mammalianpatient using a withdrawal needle 105. The blood flows from the needleinto a withdrawal bloodline 106 that is equipped with an in-linepressure sensor 107. The sensor transmits a signal indicative of theblood pressure in the withdrawal line to a computer controller 110. Thewithdrawal line loops through a blood pump 108. The pump creates asuction (negative) pressure in the withdrawal line that draws blood fromthe vein and into the line.

The pump also forces blood through a filter 111 that removes excessfluid from the blood. The filter includes a blood passage coupledbetween a blood inlet and outlet to the filter, a filtering membraneforming a portion of the walls of the passage, and a filtered fluidoutlet section on a opposite side of the membrane from the bloodpassage. The membrane is pervious to fluids, but not to blood cells andrelatively large solutes in the blood.

Some percentage of fluid (usually 10 to 20%) in the blood flowingthrough the blood passage in the filter may pass through the membrane tothe outlet section and thereby be filtered from the blood. However, theblood cells and larger proteins in the blood do not pass through thefilter membrane and remain in the blood as it exits the filter. Thefilter has a blood outlet connected to a return line 113 through whichflows blood to be infused back into a vein 102 of the patient. Thefilter has a second output through which flows separated ultrafiltrate(plasma water) that passes in a filtrate line that loops through aultrafiltrate pump 114 and into a collection bag 116.

The ultrafiltrate pump 114 is capable of generating a negative pressurein the filtrate line (and at the output side of the filter membrane) toassist the flux of ultrafiltrate across the membrane, which has asubstantial hydraulic resistance. The pressure level in the filtrateline and in the filtrate output section of the filter is determined bythe rotational speed of the ultrafiltrate pump 114. The rotational speedof pumps 108 and 114 is determined by a controller 110 that can be amicrocomputer. The controller receives pressure measurements from bloodline return sensor 112 and the ultrafiltrate pump sensor 119. Thecontroller is programmed to adjust the ultrafiltrate pump speed toprovide a pressure level in the filtrate line to achieve a desiredfiltration rate. An oxygen sensor 109 is incorporated in the bloodtubing 106 prior to the blood pump 108. Signal from the sensor 109 iscommunicated to the controller 110.

Generally, just prior to the ultrafiltration treatment, an operator,such as a nurse or medical technician, selects certain control settingson the controller for the treatment. The settings (which may be selectedby the operator or preprogrammed into the controller, or a combinationof both) may include (among other settings) a desired fluid removal ratefrom the blood. This rate may be applied by the controller to determinethe rotational speed of the ultrafiltration pump 114.

The rotational speed of the pump 114 controls the pressure (measured byultrafiltrate sensor 109) in the output section of the filter. The fluidpressure in the output section is present on one side of the filtermembrane. The fluid pressure of the blood in the blood passage ispresent on the other side of the membrane. The filtration rate isdependent on the pressure difference across the membrane of the filter.The filtration rate is controlled by the pressure in the filtrate outletsection of the filter, assuming that the blood pressure in the filterblood pressure remains constant. Accordingly, the filtration rate iscontrolled by the speed of the ultrafiltration pump 114 which determinesthe fluid pressure in the filter outlet section.

A safety feature of the controller is that it adjusts the filtrationrate to avoid hypotension of the patient. If too much fluid is removedtoo rapidly from the blood of the patient, the patient may suffer fromhypotension. To avoid hypotension, the controller monitors a feedbacksignal from the sensor 109 that detects oxygen saturation in the blood.The signal from the sensor 109 is continuously evaluated to determinewhether the patient is at risk of suffering hypotension and, if so,reducing the ultrafiltration rate or temporarily interruptingultrafiltration.

The controller 110 controls the rate of fluid removal from the blood bymodifying the rotational speed of the ultrafiltrate pump 114. Controlcan be exercised by slowly adjusting the rotational speed of the pump114 with a closed loop controller or by stopping it altogether until thevenous volume is refilled. Alternatively, the controller may cyclicallystop and start the ultrafiltration pump in a sequence of duty cycles.During a duty cycle, the pump is ON during a portion of each cycle andis OFF during the remainder of the cycle. The portion of the duty cycleduring which pump 114 is ON versus OFF determines the filtration rate.Other methods for controlling fluid removal include periodicallyclamping the ultrafiltrate line to block the output of the filter andprevent fluids from being removed from blood in the filter.

The saturation of oxygen in the blood can be measured by a non-invasivemeans of oximetry since, during the ultrafiltration, venous blood ispassed through the extracorporeal circuit. FIG. 2 shows the venous blood202 passing through the plastic tube 203 with a transparent wall. Thebiosensor consists of a photo emitter 204 and a photo receiver 201. Theemitter may be a light diode emitting light at a particular wavelength.The photo receiver is coupled with a digital signal processing (DSP)unit in the controller capable of extracting the information aboutoxygen saturation by the means well known in the field of pulseoximetry. Products for photometric pulse oximetry are available fromseveral manufactures and are well suited for detecting oxygenconcentration in a bloodline.

FIG. 3 is a chart showing venous oxygen saturation as a function of timefor a fluid overloaded patient undergoing fluid removal treatment. Ifthe fluid removal rate exceeds the refilling rate, the cardiac outputwill be reduced. Since oxygen extraction stays the same, the SvO₂ line301 declines gradually from 60% saturation. When the line crosses theallowed threshold 302, ultrafiltration is stopped by the controllerwhich is monitoring SvO₂ level based on the optical blood oxygen sensor.With the ultrafiltration being stopped, the vascular volume is graduallyrefilled, and consequently, the heart filling pressure is increased, asis cardiac output. At point 303, the process is reversed and the SvO₂starts to increase. Since point 304 is above the preset threshold,ultrafiltration is safely and automatically restarted by the controller.

FIG. 4 illustrates controlling ultrafiltration using the relative changeof a physiologic parameter such as SvO₂. At the beginning of treatment401, a baseline value is established for the physiologic parameter to bemonitored. The baseline value is expressed as 100% in the chart shown inFIG. 4. The operator determines what percentage deviation from thebaseline is allowed. In this example, a range 407 is set to 7% ofbaseline. The treatment is started. If in the course of treatment 402parameter falls below 93% of the baseline ultrafiltration is stopped (orthe ultrafiltration rate is slowed) until the condition is restored 403.Once safe condition is restored, treatment continues.

FIG. 5 illustrates an algorithm used by the ultrafiltration controllerwith an oxygen saturation feedback. The calculations for controlling theflow through the pump 114 are made in the computer—controller 110. Thecontroller receives input from the operator 118 such as a flow ratesetting. The operator may enter the desired initial rate of fluidremoval or the allowed tolerances to the change of the oxygen saturationof venous blood measured by sensor 109. At the beginning of treatment, abaseline value 501 of SvO₂ is established and stored in the computermemory. Periodically the controller measures the reading 502 of thesensor 109. Next, a deviation 503 of the reading from the storedbaseline is calculated and compared 504 to the allowed limit. If thedeviation exceeds the allowed amount, the fluid removal rate 505 isrecalculated and the rotational speed 506 of the ultrafiltrate pump 114is reduced by the predetermined amount (controller gain). Unless the endof treatment time 507 is reached, the process is repeated starting froman updated measurement 502 of oxygen in blood. More sophisticatedalgorithms can be employed if the slow continuous control of fluidremoval is desired. Well known algorithms such as PI and PID regulatorscan be employed using deviation of the SvO₂ measurement from baseline asinput and the speed of ultrafiltrate pump as the output.

FIG. 7 illustrates the electrical architecture of the ultrafiltrationcontroller system 600 (110 in FIG. 1), showing the various signal inputsand actuator outputs to the controller. The user-operator inputs thedesired ultrafiltrate extraction rate into the controller by pressingbuttons on a membrane interface keypad 609 on the controller. Other usersettings may include the maximum flow rate of blood through the system,maximum time for running the circuit to filter the blood, the maximumultrafiltrate rate the maximum allowed deviation of the venous bloodoxygen saturation from the baseline. The settings input by the user arestored in a memory and read and displayed by the controller CPU 605(central processing unit, e.g., microprocessor or micro-controller) onthe display 610.

The controller CPU regulates the pump speeds by commanding a motorcontroller 602 to set the rotational speed of the blood pump 108 to acertain speed specified by the controller CPU. Similarly, the motorcontroller adjusts the speed of the ultrafiltrate pump 114 in responseto commands from the controller CPU and to provide a particular filtrateflow velocity specified by the controller CPU.

Feedback signals from the pressure transducer sensors 611 are convertedfrom analog voltage levels to digital signals in an A/D converter 616.The digital pressure signals are provided to the controller CPU asfeedback signals and compared to the intended pressure levels determinedby the CPU. In addition, the digital pressure signals may be displayedby the monitor CPU 614.

The motor controller 602 controls the velocity, rotational speed of theblood and filtrate pump motors 603, 604. Encoders 607 and 606 mounted tothe rotational shaft of each of the motors as feedback providequadrature signals (e.g., a pair of identical cyclical digital signals,but 60° out-of-phase with one another). These signal pairs are fed to aquadrature counter within the motor controller 602 to give bothdirection and position. The direction is determined by the signal leadof the quadrature signals. The position of the motor is determined bythe accumulation of pulse edges. Actual motor velocity is computed bythe motor controller as the rate of change of position. The controllercalculates a position trajectory that dictates where the motor must beat a given time and the difference between the actual position and thedesired position is used as feedback for the motor controller. The motorcontroller then modulates the percentage of the on time of the PWMsignal sent to the one-half 618 bridge circuit to minimize the error. Aseparate quadrature counter 617 is independently read by the ControllerCPU to ensure that the Motor Controller is correctly controlling thevelocity of the motor. This is achieved by differentiating the change inposition of the motor over time.

The monitoring CPU 614 provides a safety check that independentlymonitors each of the critical signals, including signals indicative ofblood leaks, pressures in blood circuit, weight of filtrate bag, motorcurrents, air in blood line detector and motor speed/position. Themonitoring CPU has stored in its memory safety and alarm levels forvarious operating conditions of the ultrafiltrate system. By comparingthese allowable preset levels to the real-time operating signals, themonitoring CPU can determine whether a safety alarm should be issued,and has the ability to independently stop both motors and reset themotor controller and controller CPU if necessary.

Input from the Oxygen sensor 615 is converted to a digital signalsimilar to other analog signals. Alternatively, if a microprocessorbased sensor is used, it can be already in a digital form. This signalinput allows CPU 605 to recalculated the desired ultrafiltration rateand control the rotational speed of the pump 114 to prevent reduction inthe patient's cardiac output and hypotension without help from theoperator.

The preferred embodiment of the invention now known to the invention hasbeen fully described here in sufficient detail such that one of ordinaryskill in the art is able to make and use the invention using no morethan routine experimentation. The embodiments disclosed herein are notall of the possible embodiments of the invention. Other embodiments ofthe invention that are within the spirit and scope of the claims arealso covered by this patent.

What is claimed is:
 1. A method for preventing hypotension in amammalian patient whose blood is withdrawn, treated in a blood treatmentdevice having an extracorporeal blood circuit for removal ofultrafiltrate fluid, and infused into the patient, said methodcomprising: a. withdrawing blood from a peripheral vein of the patientinto the blood circuit, treating the withdrawn blood flowing through thecircuit to remove the ultrafiltrate fluid from the blood, and infusingthe treated blood into a peripheral vein of the patient; b. monitoringoxygen concentration in the blood withdrawn from the peripheral vein andflowing through the circuit; c. determining a baseline oxygenconcentration level in the blood during an initial phase of thetreatment; d. automatically reducing filtrate flow from a firstfiltration rate of the ultrafiltrate fluid extracted from blood to asecond filtration rate, if the oxygen concentration in blood varies froma predetermined target oxygen value below the baseline level, and e.automatically resuming the first filtration rate when the oxygenconcentration level returns to the baseline level.
 2. A method as inclaim 1 where oxygen concentration is measured at a peripheral veinblood withdrawal tube of the extracorporeal circulation circuit betweena patient connection and a blood pump.
 3. A method for preventinghypotension as in claim 1 wherein the initial phase of treatment isbefore the filtrate flow starts.
 4. A method for preventing hypotensionas in claim 1 wherein the oxygen concentration is determined using anoptical biosensor.
 5. A method for preventing hypotension as in claim 1wherein the oxygen concentration is applied to estimate cardiac outputand, in step d, reducing filtration if the estimated cardiac outputfalls a predetermined amount.
 6. A method for preventing hypotension asin claim 1 wherein the oxygen concentration is relative to an initialoxygen concentration level.
 7. A method for preventing hypotension as inclaim 1 wherein the oxygen concentration is an oxygen concentration ofblood in the circuit.
 8. A method as in claim 1 wherein the blood iswithdrawn from a peripheral vein of the patient and infused into aperipheral vein of the patient.
 9. A method as in claim 1 applied totreat congestive heart failure in the patient.
 10. A method as in claim1 wherein the flow rate of the ultrafiltrate is automatically adjustedto decrease the rate of filtration to maintain the oxygen level abovethe target value and to increase the rate of filtration when the oxygenlevel is at least the base line value.
 11. A method as in claim 1wherein the flow rate of the ultrafiltrate is adjusted while blood flowscontinuously through the blood treatment device.
 12. A method forpreventing hypotension in a mammalian patient whose blood is beingwithdrawn, treated in a blood treatment device of an extracorporealblood circuit for removal of ultrafiltrate fluid, and infused into thepatient, said method comprising: a. monitoring oxygen concentration inblood flowing in a peripheral blood vessel; b. automatically reducing aflow rate of the ultrafiltrate fluid extracted from blood if the oxygenconcentration in blood drops to a predetermined target value, and c.automatically increasing the reduced flow rate of the ultrafiltratefluid if the oxygen concentration in blood increases to a baselinevalue.
 13. A method for preventing hypotension in a mammalian patientwhose blood is withdrawn, treated in a blood treatment device having anextracorporeal blood circuit for removal of ultrafiltrate fluid, andinfused into the patient, said method comprising: a. withdrawing bloodfrom a peripheral vein of the patient, treating the withdrawn bloodflowing through the circuit to remove the ultrafiltrate fluid from theblood and infusing the treated blood into a peripheral vein of thepatient; b. monitoring oxygen concentration in the blood withdrawn fromthe peripheral vein and flowing through the circuit; c. determining abaseline oxygen concentration level in the withdrawn blood during aninitial phase of the treatment; d. automatically reducing filtrate flowfrom a first rate of the ultrafiltrate fluid to a reduced rate if theoxygen concentration in blood varies from a predetermined target oxygenvalue, wherein the predetermined target oxygen value is a function ofthe baseline level, and wherein the oxygen concentration is a mixedvenous oxygen saturation (SvO₂) level.
 14. A method for preventinghypotension as in claim 13 wherein the oxygen concentration is a venousoxygen saturation (SvO₂) level of blood taken from a peripheral vein.15. A method for preventing hypotension as in claim 13 wherein thetarget value is a sum of the baseline level and a predetermined oxygenchange value.
 16. A method for preventing hypotension as in claim 15wherein the predetermined change value is a percentage of the baselinelevel.
 17. A method for preventing hypotension as in claim 15 whereinthe predetermined change value is no greater than a seven percent lessthan the baseline level.
 18. A method of controlling an extracorporealblood circuit comprising: a. withdrawing blood from a withdrawal bloodvessel in a patient into the extracorporeal circuit; b. filtering fluidsfrom blood flowing through the circuit at a controlled filtration rate;c. detecting a reduction in cardiac output level of the patient, whereinthe reduction in cardiac output level is determined by monitoring oxygenlevel of venous blood in or taken from a peripheral vein of the patient;d. automatically reducing the filtration flow rate if the measuredcardiac output falls below a first threshold level, and e. automaticallystopping the filtration flow rate if, after step d, the measured cardiacoutput falls below a second threshold level, wherein the secondthreshold level is below the first threshold level.
 19. A method ofcontrolling an extracorporeal blood circuit as in claim 18 wherein theblood circuit includes an oxygen saturation sensor having an emitter anda receiver mounted on opposite sides of a bloodline of said circuit. 20.A method of controlling an extracorporeal blood circuit as in claim 18,further comprising increasing the filtration flow after step (d) if themeasured cardiac output rises above a second threshold level higher thanthe first threshold level.
 21. A method of controlling an extracorporealblood circuit as in claim 18 wherein the controlled filtration rate isreduced by slowing an ultrafiltration pump.
 22. A method of controllingan extracorporeal blood circuit as in claim 18 wherein the controlledfiltration rate is determined by cyclically starting and stopping thefiltration of fluids in accordance with a duty cycle, and the filtrationrate is reduced by reducing an ON period of the duty cycle.